Evidence map›Paper›PMID 25573745›Full record

ArticleMolecular & cellular proteomics : MCP2015

Proteomics-based metabolic modeling reveals that fatty acid oxidation (FAO) controls endothelial cell (EC) permeability.

Francesca Patella, Zachary T Schug, Erez Persi, Lisa J Neilson, Zahra Erami, Daniele Avanzato, Federica Maione, Juan R Hernandez-Fernaud, Gillian Mackay, Liang Zheng and 8 more

Open access · hybridAbstract read
In one paragraph

Article in Molecular & cellular proteomics : MCP, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
65citing papers in PubMed, 1 pooled it
5.1field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

65 citing papers in PubMed, 1 synthesis or guideline pooled it, 112 citations in OpenAlex.

  1. Preclinical techniques to investigate exercise training in vascular pathophysiology.American journal of physiology. Heart and circulatory physiology · 2021
    Pooled it
  2. Review
  3. Article
  4. Review
  5. Endothelial Metabolic Reprogramming Links Diabetes to Atherosclerosis.Diabetes, metabolic syndrome and obesity : targets and therapy · 2026
    Review
  6. Review
  7. Review
  8. Article
  9. Review
  10. Review
  11. Article
  12. Article
  13. Article
  14. Metabolic Responses to Redox Stress in Vascular Cells.Antioxidants & redox signaling · 2024
    Review
  15. Article
  16. Article
  17. Article
  18. Article
  19. Review
  20. Article

5 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

18 authors at 6 institutions in 3 countries.

Francesca PatellaFrom the ‡Vascular Proteomics Lab.
Zachary T Schug§Apoptosis and Tumour Metabolism Lab.
Erez Persi¶The Blavatnik School of Computer Science, Tel Aviv University, 69978 Tel Aviv, Israel; ‖School of Physics and Astronomy, Tel Aviv University, 69978 Tel Aviv, Israel;
Lisa J NeilsonFrom the ‡Vascular Proteomics Lab.
Zahra Erami**Tumour Cell Migration Lab, Cancer Research UK Beatson Institute, Switchback Road, G61 1BD, Glasgow, UK;
Daniele Avanzato‡‡Department of Life Sciences and Systems Biology, University of Torino, Via Accademia Albertina 13, 10123 Torino, Italy;
Federica Maione§§Laboratory of Transgenic Mouse Models, Candiolo Cancer Institute - FPO, IRCCS, Str prov 142 Km 3.95, 10060, Candiolo, Torino, Italy; ¶¶Department of Science and Drug Technology, University of Torino, Via P. Giuria, 9 - 10125 Torino, Italy;
Juan R Hernandez-FernaudFrom the ‡Vascular Proteomics Lab.
Gillian Mackay§Apoptosis and Tumour Metabolism Lab.
Liang Zheng§Apoptosis and Tumour Metabolism Lab.
Steven ReidFrom the ‡Vascular Proteomics Lab.
Christian Frezza‖‖MRC Cancer Unit, Cambridge Biomedical Campus, University of Cambridge, Hutchison/MRC Research Centre, Box 197, CB2 0XZ, Cambridge, UK;
Enrico Giraudo§§Laboratory of Transgenic Mouse Models, Candiolo Cancer Institute - FPO, IRCCS, Str prov 142 Km 3.95, 10060, Candiolo, Torino, Italy; ¶¶Department of Science and Drug Technology, University of Torino, Via P. Giuria, 9 - 10125 Torino, Italy;
Alessandra Fiorio Pla‡‡Department of Life Sciences and Systems Biology, University of Torino, Via Accademia Albertina 13, 10123 Torino, Italy;
Kurt Anderson**Tumour Cell Migration Lab, Cancer Research UK Beatson Institute, Switchback Road, G61 1BD, Glasgow, UK;
Eytan Ruppin¶The Blavatnik School of Computer Science, Tel Aviv University, 69978 Tel Aviv, Israel; Sackler School of Medicine, and Department of Molecular Microbiology and Biotechnology, Faculty of Life Sciences, Tel-Aviv University, 69978 Tel Aviv, Israel.
Eyal Gottlieb§Apoptosis and Tumour Metabolism Lab.
Sara ZanivanFrom the ‡Vascular Proteomics Lab, s.zanivan@beatson.gla.ac.uk.
Brain Tumour Charity · GBAccademia Albertina delle Belle Arti · ITCancer Research UK Scotland Institute · GBCandiolo Cancer Institute · ITTel Aviv University · ILUniversity of Cambridge · GB

Funding

Cancer Research UK 12935Cancer Research UK 15565Cancer Research UK 18278Medical Research Council MC_UP_1101/3Medical Research Council MC_UU_12022/6
6 · The paper itself

Abstract

Endothelial cells (ECs) play a key role to maintain the functionality of blood vessels. Altered EC permeability causes severe impairment in vessel stability and is a hallmark of pathologies such as cancer and thrombosis. Integrating label-free quantitative proteomics data into genome-wide metabolic modeling, we built up a model that predicts the metabolic fluxes in ECs when cultured on a tridimensional matrix and organize into a vascular-like network. We discovered how fatty acid oxidation increases when ECs are assembled into a fully formed network that can be disrupted by inhibiting CPT1A, the fatty acid oxidation rate-limiting enzyme. Acute CPT1A inhibition reduces cellular ATP levels and oxygen consumption, which are restored by replenishing the tricarboxylic acid cycle. Remarkably, global phosphoproteomic changes measured upon acute CPT1A inhibition pinpointed altered calcium signaling. Indeed, CPT1A inhibition increases intracellular calcium oscillations. Finally, inhibiting CPT1A induces hyperpermeability in vitro and leakage of blood vessel in vivo, which were restored blocking calcium influx or replenishing the tricarboxylic acid cycle. Fatty acid oxidation emerges as central regulator of endothelial functions and blood vessel stability and druggable pathway to control pathological vascular permeability.

Indexed as

MetabolomeModels, BiologicalAdenosine TriphosphateAnimalsCarnitine O-PalmitoyltransferaseEndothelial CellsEpoxy CompoundsFatty AcidsHumansHuman Umbilical Vein Endothelial CellsIn Vitro TechniquesMiceOxidation-ReductionOxygen ConsumptionPermeabilityProteomicsAdenosine TriphosphateCarnitine O-PalmitoyltransferaseCPT1A protein, humanEpoxy CompoundsetomoxirFatty Acids

Identifiers

PMID25573745
PMCPMC4349982
OpenAlexW2158468020

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.